Medicine and Health Sciences Commons^™

Dissecting The Potential Mechanisms Of Histone Deacetylase 1 Dependent Macrophage Phagocytosis Of Mycobacterium Tuberculosis, Owusu A. Christian

Biotechnology Theses

Histone deacetylases (HDACs) mediate the removal of acetyl groups from the histones of chromatin and regulate the expression of the genes involved in cancer development and immune cell functions. Our previous study showed that HDAC2 enhances IL-1β production by Mycobacterium tuberculosis (Mtb) infected macrophages by promoting inflammasome activation. HDAC1, on the other hand, regulates macrophage phagocytosis of Mtb. However, the mechanisms by which HDAC1 controls macrophage phagocytosis remain unclear.

Using human monocyte-derived macrophages (MDMs) and Mtb strains, we explore the mechanism of HDAC1 in macrophage phagocytosis of Mtb. Our results showed that blocking HDAC1, either chemically or genetically, …

A Pilot Project For Tuberculosis Education In College Students, Sarah Williams

Doctor of Nursing Practice Final Manuscripts

Background: San Diego’s Tuberculosis (TB) incidence is more than double the national rate. The majority of cases of active TB are due to the progression of latent TB infection (LTBI).

Objectives: This evidence-based practice (EBP) project aimed to increase knowledge, awareness, and improve attitudes and practices regarding TB among college students.

Participants: Twenty Community College Students in San Diego participated in the project.

Methods: Students attended an in-person educational session. A pre-post knowledge, attitudes and practices (KAP) questionnaire measured the impact.

Results: The intervention improved knowledge and attitudes. The average post-intervention TB knowledge score was 95.8% compared to 57% …

Pkpd-Model Based Preclinical Characterization Of The Activity Of Spectinamide 1599 Against Mycobacterial Subpopulations. And The Identification Of Potential Partners For Combination Therapy, Zaid Hanif Temrikar

Theses and Dissertations (ETD)

Tuberculosis is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent prior to COVID19. Mycobacterium tuberculosis (Mtb) is the causative agent of TB. The interaction between Mtb and the immune system leads to development of diverse environmental niches and physiology within the lung of the TB patients. Mtb is thought to adapt and thrive in such an environment by transforming to different phenotypic variants. Such variants are difficult to kill and are thought to prolong TB pharmacotherapy. Spectinamide 1599 is a synthetic modification of spectinomycin that has demonstrated excellent …

Testing Of Indazole Inhibitors Of Kasa, A Vital Enzyme Of M. Tuberculosis, Karissa Highlander

Student Research Submissions

Tuberculosis is a disease that affects the lungs caused by Mycobacterium tuberculosis (M. tuberculosis). Although drug treatment options exist, increased rates of antibiotic resistant strains have become more prevalent in recent years, driving a need for new treatment approaches. KasA, a β-ketoacyl synthase, has been found to synthesize parts of the cell wall and been identified as an attractive drug target. Previous medicinal chemistry research has been completed to synthesize six effective competitive inhibitors of KasA that would potentially block the enzyme from binding the substrate, preventing elongation of the backbone and creation of the mycolic fatty acids that …

Relationship Between Homelessness, Substance Use, Employment, Living On A Reservation And Tuberculosis Among Northern Plains Native Americans, Darla Mccloskey

Walden Dissertations and Doctoral Studies

Native Americans in the Northern Plains have a long history of tuberculosis (TB) infections. There is limited research on the causes of latent TB infections (LTBI) and TB in this population. The purpose of this quantitative study was to assess the relationship between latent TB and factors of homelessness, substance use, employment, living on a reservation, and active or latent TB among this population using the eco-social theory as the theoretical framework. Data from 146 TB cases of Native Americans living in the Northern Plains and diagnosed with TB from 1999 to 2019 were analyzed using chi-square tests that showed …

Relationship Between Homelessness, Substance Use, Employment, Living On A Reservation And Tuberculosis Among Northern Plains Native Americans, Darla Mccloskey

Walden Dissertations and Doctoral Studies

Native Americans in the Northern Plains have a long history of tuberculosis (TB) infections. There is limited research on the causes of latent TB infections (LTBI) and TB in this population. The purpose of this quantitative study was to assess the relationship between latent TB and factors of homelessness, substance use, employment, living on a reservation, and active or latent TB among this population using the eco-social theory as the theoretical framework. Data from 146 TB cases of Native Americans living in the Northern Plains and diagnosed with TB from 1999 to 2019 were analyzed using chi-square tests that showed …

Relationship Between Homelessness, Substance Use, Employment, Living On A Reservation And Tuberculosis Among Northern Plains Native Americans, Darla Mccloskey

Walden Dissertations and Doctoral Studies

Native Americans in the Northern Plains have a long history of tuberculosis (TB) infections. There is limited research on the causes of latent TB infections (LTBI) and TB in this population. The purpose of this quantitative study was to assess the relationship between latent TB and factors of homelessness, substance use, employment, living on a reservation, and active or latent TB among this population using the eco-social theory as the theoretical framework. Data from 146 TB cases of Native Americans living in the Northern Plains and diagnosed with TB from 1999 to 2019 were analyzed using chi-square tests that showed …

Il-27 Negatively Impacts Immunity Developed Following Bcg Administration, Shelby D. Bradford

Graduate Theses, Dissertations, and Problem Reports

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a predominantly respiratory pathogen responsible for over ten million infections and one million deaths last year. Despite it being a primary objective of the World Health Organization (WHO) for several decades to irradicate TB, progress toward this objective has fallen short of the 2020 target to end TB by 2035. Meeting this goal will require advancements in diagnostic tools, education, healthcare access, and treatments and preventatives. Regarding prevention, the primary tool for this strategy is through vaccination. Currently, the only licensed vaccine for protection against TB is the century old …

Expansion On The Use Of The Novel Compound, Elp-004, Using A Mycobacterium Tuberculosis Experimentation Model, Kendyl Marie Berry

Graduate Theses, Dissertations, and Problem Reports

Osteoarticular tuberculosis (OAT) is a bone degenerative disease that results in bone erosion, joint effusion, joint swelling, and sometimes, nerve compression. OAT occurs from the hematogenous dissemination of Mycobacterium tuberculosis (Mtb) bacilli spreading from the primary site of infection to the bones and joints; the primary site of infection tends to be the lungs as pulmonary tuberculosis infections are the most common. OAT can occur as the result of an active or latent infection. Latent infections result in OAT when bacilli are able to escape granulomas. The incidence of OAT is not as high as pulmonary infections, making up about …

Evaluation Of Healthcare Facilities And Services Provided For Tuberculosis And Zoonotic Tuberculosis In Kajiado County, Kenya, Joel Zhang

Electronic Thesis and Dissertation Repository

There are key challenges people face due to the burden of tuberculosis (TB), caused by Mycobacterium tuberculosis, and zoonotic tuberculosis (ZTB), caused by Mycobacterium bovis, in Kenyan Maasai rural communities. Thus, the objective of this study was to describe current capacities/infrastructure for diagnosis/treatment of TB/ZTB, and knowledge, attitudes, and practices among healthcare workers in rural Kajiado, Kenya.

Discovery Of Ojt008 As A Novel Inhibitor Of Mycobacterium Tuberculosis, Collins Chidi Onyenaka

Dissertations (2016-Present)

Despite recent progress in the diagnosis of Tuberculosis (TB), the chemotherapeutic management of TB is still challenging. Mycobacterium tuberculosis (Mtb) is the etiological agent of TB, and TB is classified as the 13th leading cause of death globally [WHO 2021]. 558,000 people were reported to develop multi-drug resistant TB globally [WHO 2020]. Our research focuses on targeting Methionine Aminopeptidase (MetAP), an essential protein for the viability of Mtb. MetAP is a metalloprotease that catalyzes the removal of N-terminal methionine (NME) during translation of protein [Giglione et al., 2003]. This essential role of MetAPs makes this enzyme an auspicious target for …

Treatment Outcomes And Associated Factors In Tb/Hiv-Coinfected Patients In Namibia, Esland Shilongo

Walden Dissertations and Doctoral Studies

AbstractHIV and TB have merged into a deadly co-epidemic in Namibia. Currently, though, TB and HIV data at the national, regional, and district level might be underreported and insufficient to understand the full burden and outcome rates of TB and HIV. Targeting the TB outcomes rate among TB/HIV-coinfected individuals is an effective strategy for decreasing future TB burden and furthering the gains in the control of both diseases. The objective of this study was: to assess the outcomes of patients registered for anti-TB treatment in //Karas Region which has the largests burden of TB in Namibia. A 5-year retrospective cohort …

Assessment Of Multidrug Resistance Among Tuberculosis Patients In Lesotho, Jerry Yakubu Yahaya

Walden Dissertations and Doctoral Studies

The emergence of multidrug-resistant tuberculosis (MDR-TB) jeopardizes the tremendous efforts in the fight against tuberculosis in Lesotho. To understand the occurrence of MDR-TB, it is important to identify the associated risk factors and how to address them. There is a literature gap on the sociodemographic risk factors associated with MDR-TB in Lesotho. This study assessed whether there is any significant association between age, employment, income, sex, education, place of residence and MDR-TB. The association between HIV and MDR-TB was also evaluated. Guided by the health belief model and social cognitive theory, a retrospective case-control study design and a proportionate stratified …

From Isolation To Inclusion: Embracing Local Perspectives In Examining The Treatment Model Of Care For Aboriginal Persons Affected By Tuberculosis Or Leprosy In The Kimberley Region, North Western Australia, Stefanie Jane Oliver

Theses

In the remote Kimberley region of North Western Australia, tuberculosis (TB) and leprosy continue to affect a small number of Aboriginal people, despite historical efforts to eliminate either disease. Treatment, predominantly antibiotic therapy, is a principal therapeutic intervention used to cure TB and leprosy and halt infection transmission. Decisions made around treatment therefore impact not only the individual person affected, but also their families and communities. The well-worn models of Directly Observed Therapy (DOT) and case management are used nationally to assist treatment continuity and completion. Neither model has been substantiated for cultural appropriateness nor for meeting the specific needs …

Exploring The Interaction Of Amphiphilic Mycobacterial Lipoarabinomannan With Lipoproteins: Implications For Blood-Based Diagnosis, Shailja Jakhar

Biomedical Sciences ETDs

Currently, over one-third of the global population is infected with tuberculosis (TB), one of the world’s most deadly infectious diseases. The current gold standard for TB diagnosis is microbiological culture, which can take up to 6-8 weeks, which is not conducive to timely treatment. There are no reliable diagnostics for TB. Disease manifestation and outcome of diagnostic tests for TB are influenced by co-morbidities such as HIV co-infection, further complicating diagnostics development. Thus, there is a need for reliable diagnostics for TB. This is especially true in pediatric populations where the differential disease presentation further complicates outcomes.

This dissertation describes …

Examining Early Interactions Between Innate Airway Resident Immune Cells And Mtb-Specific Factors During Pulmonary Infection With Mycobacterium Tuberculosis, Micah D. Dunlap

Arts & Sciences Electronic Theses and Dissertations

Mycobacterium tuberculosis (Mtb) is the leading cause of death by an infectious agent in the world today, infecting roughly one quarter of humans. Despite this, the mechanisms of early pathogenesis and host protective innate immune responses remain poorly understood and uncharacterized.

Lung resident Alveolar Macrophages (AMs) are the first host contact with Mtb bacilli after inhalation and are thus key mediators of the early pulmonary immune response. AMs are generally believed to reside entirely in the airway, but it was recently demonstrated that they have the capacity to egress and enter into granulomas during pulmonary infection with hypervirulent Mtb. Furthermore, …

Glycolytic Myeloid Cells Protect The Host In Tuberculosis, Hayden Thomas Pacl

All ETDs from UAB

Despite curative treatment, tuberculosis remains a leading cause of death around the world. As such, there is great interest in novel therapeutic approaches to treat this disease. One such approach aims to enhance the efficacy of host immune cells in responding to the pathogen, Mycobacterium tuberculosis—so called host-directed therapies. The metabolism of immune cells has been a central focus in the search for hostdirected therapies, and the role of glycolysis in myeloid cells, in particular, has received much attention. However, the role of glycolysis in myeloid cells in the context of tuberculosis has not yet been made clear. Here we …

Improving Latent Tuberculosis Infection (Ltbi) Screening And Treatment In A School-Based Setting, Andrea Bell

Doctor of Nursing Practice Final Manuscripts

Abstract

Background: San Diego County’s tuberculosis (TB) incidence rate is nearly double than the national rate. In 2019, there have been 5 cases of active TB in the county’s public high schools, which have demonstrated the need for prevention interventions in this setting.

Objectives: This evidence-based project is aimed to increase awareness, screening and treatment of latent TB infection (LTBI) in the school setting.

Methods: A TB risk assessment form and consent was sent in the registration packets. A one-time TB educational presentation was given to high school freshman students with a pretest and posttest. For students at-risk, a confidential …

Design And Synthesis Of Novel Analogs As Potential Antitubercular Agents, Peggy Mccluggage

Honors Theses

Tuberculosis (TB) is an infectious, airborne disease which primarily infects the lungs. One-third of the world’s population is currently estimated to be infected with Mycobacterium tuberculosis (Mtb), the causative agent for TB [1]. Current treatment for this disease requires at least six months of taking multiple antibiotics with undesirable side effects [2]. Difficulty in complying to this regimen as well as the prevalence of HIV/AIDS has led to antimicrobial resistance seen in Mtb. In order to combat the Multi-Drug Resistant and Extensively-Drug Resistant strains of the disease-causing bacteria, preventative care and novel antibiotics are urgently needed [3]. The purpose for …

Surveying Tuberculosis Screening Practices Of South Carolina Hospital Employees, Tamara T. Carree

Theses and Dissertations

BACKGROUND: Every year tuberculosis (TB) causes over 10 millions of people globally and in recent years has caused over 9,000 cases annually in the United States. TB can be transmitted in hospital settings, and South Carolina hospitals, like hospitals elsewhere in the country maintain a responsibility to test their employees for this disease. Nosocomial infections of active TB among patients and healthcare workers can be burdensome on hospital resources. Testing healthcare workers and implementing prevention strategies are examples of administrative controls provided in the 2005 guidelines by the Centers for Disease Control and Prevention (CDC). Implementation of administrative controls are …

A Prospective Cohort Study To Evaluate The Efficacy Of A Peer-Led Tuberculosis Education And Counseling Intervention In Kampala, Uganda, Anna Dawn Baker

Public Health Theses

Tuberculosis (TB) is one of the leading causes of death worldwide and disproportionally burdens low- to middle-income countries (LMICs). Upon initiation of treatment for an active TB diagnosis, universal TB education and counseling (TEC) is recommended to promote knowledge and medication adherence. Though previous studies have shown that there are areas that can be improved when delivering routine TEC, there is limited data on how peer-led TEC can fill these gaps in Kampala, Uganda. Our study evaluated the efficacy of a peer-led TEC intervention among newly diagnosed adults initiating TB treatment in Kampala and assessed capacity for scale-up. We used …

Measuring Tb Stigma In Kampala, Uganda, Amber James

Public Health Theses

Tuberculosis (TB) is one of the leading causes of death worldwide and adversely affects persons living with HIV. TB is a highly stigmatizing disease and has been shown to interfere in household TB contact investigation. The objective of this study was to investigate the severity and characteristics of TB stigma through a multiple methods approach. Quantitative methods involved distributing Van Rie Stigma Scales validated in Southeast to household contacts of Index TB patients during routine household TB contact investigation. Qualitative methods involved interviewing household contacts about their attitudes towards household contact investigation, knowledge of TB transmission and treatment, and perceptions …

Geospatial Analysis Of Drug-Resistant Tuberculosis In Santiago De Cali, Colombia, Oscar Norberto Perales

Public Health Theses

Infectious diseases like tuberculosis are undergoing an epidemiological transformation in developing countries such as Colombia and throughout Latin America. Recent economic and social developments may drive heterogeneous burdens of disease in the region, especially in urban settings. Geographic Information Systems (GIS) may allow us to better appreciate the geospatial distributions of TB in these contexts. In this study, we aimed to identify regions in Santiago de Cali facing disproportionate TB burdens and sought to determine whether the distribution of drug resistant TB differed. Additionally, we aimed to identify patient risk factors that could lead to differential drug resistance testing. This …

Tuberculosis Diagnostics In Ethiopia: Assessment Of Laboratory Procedural Capabilities And Limitations, Yeshimebet Retta

Walden Dissertations and Doctoral Studies

Abstract

Tuberculosis (TB) is a curable and preventable disease; however, in 2015, 10.4 million people were diagnosed with TB, making it one of the top 10 causes of mortality. A major part of the TB disease burden is carried by low and middle-income countries. In Ethiopia, which ranks 15th among 22 countries with a high burden of TB and multidrug resistant TB (MDR-TB), important diagnostic and treatment gaps persist. This quantitative descriptive study was primarily aimed to determine levels of adherence to standardized TB laboratory procedures by calculating and reporting the number of sputum samples, and reporting valid and documented …

Evaluation Of The Impact Of An Educational Intervention Aimed At Improving Tuberculosis Infection Control Knowledge Among Health Care Workers In A Military Treatment Facility: A Quality Improvement Project, Allen C. Potter

Graduate Theses, Dissertations, and Problem Reports

Background: Florida (FL) is one of the top five states in the nation for Tuberculosis (TB) infections. A majority of new infections can be found in the minority populations which represents 78% of all TB infections in the state. A combination of TB rates in FL, Orlando located 60 miles away and a transient population who frequently deploys worldwide to austere locations may result in an increased risk of acquiring TB. Literature suggests Health Care Providers (HCPs) obtain training regarding TB Infection Control (TB-IC). The Patrick AFB Military Treatment Facility (MTF) lacked a TB Infection Control (TB-IC) plan. Objective: The …

The Impact Of The Residency Area On Risk Factors For Tuberculosis Among People Living In Three Different Regions Of Kazakhstan, Assel Bukharbayeva

Legacy Theses & Dissertations (2009 - 2024)

Background and introduction:

Tuberculosis, Jessica Puri

Nursing Student Class Projects (Formerly MSN)

Tuberculosis (TB) is a curable disease that claims the lives of millions each year. TB is an airborne disease spread by inhaling droplets of the tubercle bacillus. There are two different types of TB related conditions; latent TB infection and active TB disease. During latent TB, an individual inhales droplets of tubercle bacillus but the immune system can fight off this infection. However, once droplets of tubercle bacillus penetrate the alveoli, and colonization of droplets multiply, latent TB transitions into active TB disease (Katanekwa & Dahlback, 2016, p. 9). TB is typically found in the lungs but can also develop …

Strategies To Combat Drug-Resistant Tuberculosis: Inhalable Microparticles Formulated With Anti-Tubercular Antibiotics And Efflux Pump Inhibitors, Elliott K. Miller

Pharmaceutical Sciences ETDs

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen which can remain dormant within the human body for years (latent tuberculosis), and once active requires extensive multidrug therapies for treatment. Long-term antibiotic(s) exposure have led to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains which require novel treatment approaches to combat Mtb resistance. Mtb may also utilize efflux pumps to expel antibiotics and promote bacterial survival, potentially mediating drug tolerance, which has been hypothesized to contribute to antibiotic resistance. Efflux pump inhibitors (EPIs) such as verapamil (VER) may potentiate effects of first-line anti-tubercular drugs (ATDs) such as rifampicin …

A Pilot Project For School-Based Screening And Treatment Of Latent Tb Infection Among Freshman High School Students, Isis Cunningham

Doctor of Nursing Practice Final Manuscripts

Background: San Diego’s tuberculosis (TB) incidence is 2.5 times higher than the national rate. Five cases of active TB in the county’s public high schools during 2018 demonstrated the need for prevention interventions in this setting.

Objectives: This evidence-based project aimed to increase awareness, screening, and treatment of latent TB infection (LTBI) in the school setting.

Methods: A one-time TB educational presentation was given to high school freshman students with a pretest and posttest. A TB risk assessment and consent was sent home with the students. For at-risk students, a confidential package was sent to the parents recommending testing along …

Selling Childhood: How The Middle Class Used Children In The Anti-Tuberculosis Movement (1930s-1940s), Hannah Fisher

Senior Theses

During the anti-tuberculosis movement of the 1930s and 1940s, children were chosen as focal points, with their roles shaped by society’s changing view of childhood, the emergence of the middle class, and the socioeconomic and political climate. Children were used by middle-class reformers as conduits through which to disseminate information and enact controls on the working class. Health education in schools had two main goals: (1) for educated children to become educated adults, and (2) for educated children to transform the behaviors of adults around them. Although researchers have studied middle-class interventions into children’s health, few have analyzed the role …